The cytological diagnosis of malignant lymphoma can be extremely difficult because the cytological features of the malignant cells in small cell and mixed small and large cell lymphomas may be indistinguishable from those of reactive lymphoid cells. We have examined the usefulness of the avidin biotin immunoperoxidase technique and a battery of antibodies to T and B cell markers to the diagnosis of lymphoma in cytological specimens. We conclude that immunocytochemistry is very useful in the cytological diagnosis of non-Hodgkin's lymphoma. Further, it is possible to diagnose the vast majority of lymphomas using only the immunoglobulin light chain markers k and l and the T-cell markers Leu-l, Leu-2, and Leu-3. We are extending the utilization of lymphoid markers to fine needle aspiration specimens of lymph nodes. Fine needle aspiration may obviate the need for repeat biopsies in patients with recurrent lymphoma.